Hong In Seok, Greenberg Marc M
Department of Chemistry, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
J Am Chem Soc. 2005 Aug 3;127(30):10510-1. doi: 10.1021/ja053493m.
DNA is the target of many anti-cancer therapies. These agents damage the biopolymer by oxidation or by alkylation. Interstrand DNA cross-links are believed to be the source of cytotoxicity of anti-tumor agents, such as mitomycin C, which alkylate the biopolymer. In contrast, deoxyguanosine oxidation is the result of reaction between DNA and singlet oxygen, which is the damaging species produced in photodynamic therapy. We have shown that, upon oxidation by singlet oxygen, an analogue of thymidine (2) rearranges to a methide, which forms DNA-DNA interstrand cross-links. This novel process suggests that 2 may be a useful adjuvant in photodynamic therapy.
DNA是许多抗癌疗法的靶点。这些药物通过氧化或烷基化作用破坏这种生物聚合物。链间DNA交联被认为是抗肿瘤药物（如丝裂霉素C，它使生物聚合物烷基化）细胞毒性的来源。相比之下，脱氧鸟苷氧化是DNA与单线态氧反应的结果，单线态氧是光动力疗法中产生的损伤性物质。我们已经表明，胸腺嘧啶类似物（2）在被单线态氧氧化后会重排为叶立德，进而形成DNA-DNA链间交联。这一新过程表明2可能是光动力疗法中一种有用的佐剂。
